ArticleThe Journal of clinical investigation2021
Dysregulation of PI3K and Hippo signaling pathways synergistically induces chronic pancreatitis via CTGF upregulation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- The Hippo signaling pathway modulates pancreatic tissue homeostasis.Cell death discovery · 2025Review
- Ovalbumin Peptide-Selenium Nanoparticles Alleviate Immune Suppression in Cyclophosphamide-Induced Mice: A Combined Transcriptomic and Proteomic Approach to Reveal the Mechanism.Foods (Basel, Switzerland) · 2025Article
- Exploring the role of YAP1 and TAZ in pancreatic acinar cells and the therapeutic potential of VT-104 in pancreatic inflammation.Journal of pancreatology · 2025Article
- Sodium aescinate promotes apoptosis of pancreatic stellate cells and alleviates pancreatic fibrosis by inhibiting the PI3K/Akt/FOXO1 signaling pathways.Frontiers in pharmacology · 2025Article
- Article
- FRA1 controls acinar cell plasticity during murine KrasDevelopmental cell · 2024Article
- Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).Molecular medicine reports · 2024Review
- Role of Hippo pathway dysregulation from gastrointestinal premalignant lesions to cancer.Journal of translational medicine · 2024Review
- Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis.Biomedicines · 2024Review
- Rescue of murine hind limb ischemia via angiogenesis and lymphangiogenesis promoted by cellular communication network factor 2.Scientific reports · 2023Article
- Pancreatic acinar cell fate relies on system xCell death & disease · 2023Article
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
- 5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro.International journal of molecular sciences · 2023Article
- Review
- Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis.Frontiers in immunology · 2022Article
- Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of PI3K and Hippo signaling in chronic pancreatitis (CP) pathogenesis is unclear. Therefore, we assessed the involvement of these pathways in CP by examining the PI3K and Hippo signaling components PTEN and SAV1, respectively. We observed significant decreases in pancreatic PTEN and SAV1 levels in 2 murine CP models: repeated cerulein injection and pancreatic ductal ligation. Additionally, pancreas-specific deletion of Pten and Sav1 (DKO) induced CP in mice. Pancreatic connective tissue growth factor (CTGF) was markedly upregulated in both CP models and DKO mice, and pancreatic CCAAT/enhancer-binding protein-α (CEBPA) expression was downregulated in the CP models. Interestingly, in pancreatic acinar cells (PACs), CEBPA knockdown reduced PTEN and SAV1 and increased CTGF levels in vitro. Furthermore, CEBPA knockdown in PACs induced acinar-to-ductal metaplasia and activation of cocultured macrophages and pancreatic stellate cells. These results were mitigated by CTGF inhibition. CP in DKO mice was also ameliorated by Ctgf gene deletion, and cerulein-induced CP was alleviated by antibody-mediated CTGF neutralization. Finally, we observed significantly decreased PTEN, SAV1, and CEBPA and increased CTGF levels in human CP tissues compared with nonpancreatitis tissues. Taken together, our results indicate that dysregulation of PI3K and Hippo signaling induces CP via CTGF upregulation.
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